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PR00561

Identifier
ADRENRGCB1AR  [View Relations]  [View Alignment]  
Accession
PR00561
No. of Motifs
7
Creation Date
15-AUG-1996  (UPDATE 28-JUL-1999)
Title
Beta-1 adrenergic receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01103 ADRENERGICR
INTERPRO; IPR000507
GCRDB; GCR_0048; GCR_0578; GCR_0126; GCR_0127
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
 
2. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
G protein-coupled receptor fingerprints.
7TM, VOLUME 2, EDS. G.VRIEND AND B.BYWATER (1993).
 
3. BIRNBAUMER, L.
G proteins in signal transduction.
ANNU.REV.PHARMACOL.TOXICOL. 30 675-705 (1990).
 
4. CASEY, P.J. AND GILMAN, A.G.
G protein involvement in receptor-effector coupling.
J.BIOL.CHEM. 263(6) 2577-2580 (1988).
 
5. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Design of a discriminating fingerprint for G protein-coupled receptors.
PROTEIN ENG. 6(2) 167-176 (1993).
 
6. WATSON, S. AND ARKINSTALL, S.
Adrenaline and noradrenaline.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp32-54.

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that 
encompasses a wide range of functions (including various autocrine, para-
crine and endocrine processes). They show considerable diversity at the 
sequence level, on the basis of which they can be separated into distinct 
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship, 
but between which there is no statistically significant similarity in 
sequence [1]. The currently known clan members include the rhodopsin-like 
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating
pheromone receptors, and the metabotropic glutamate receptor family.
 
The rhodopsin-like GPCRs themselves represent a widespread protein family 
that includes hormone, neurotransmitter and light receptors, all of
which transduce extracellular signals through interaction with guanine
nucleotide-binding (G) proteins. Although their activating ligands vary 
widely in structure and character, the amino acid sequences of the 
receptors are very similar and are believed to adopt a common structural 
framework comprising 7 transmembrane (TM) helices [3-5]. 
 
In the periphery, the adrenergic system plays an important role in
regulating the cardiovascular system [6]. Increased sympathetic discharge
to the heart increases the rate and force of contraction mediated through 
beta-1 receptors. Circulating adrenaline also acts on cardiac tissue, and, 
in addition acts both on alpha-1 adrenoceptors in arterial smooth muscle, 
stimulating vasoconstriction, and on beta-2 adrenoceptors in vascular beds 
of skeletal muscle, stimulating vasodilation [6]. In the CNS, noradrenaline 
is thought to be involved in the regulation of mood, and various psycho-
active drugs alter noradrenergic function. Numerous drugs exert their 
actions via adrenoceptors: e.g., beta-2 selective agonists such as 
salbutamol are used in the acute treatment of asthma, while alpha agonists 
prolong the action of local anaesthetics, and act as nasal decongestants [6].
 
Adrenoceptors can be divided into three main classes based on sequence
similarity, receptor pharmacology and signalling mechanisms. Further 
subdivisions exist within each class [6]. A large number of agonists and 
antagonists distinguish between the different classes of adrenoceptor; by
contrast, relatively small differences in agonist and antagonist affinities
are demonstrated, especially within the alpha-1 and alpha-2 adrenoceptor
subtypes [6]. 
 
Beta-1 and beta-2 receptors often coexist, but one subtype normally
predominates [6]. Beta-1 receptors are the predominant subtype in cardiac
tissue (where they mediate positive inotropic and chronotropic effects) and
in the kidney (where they enhance renin release) [6]. The receptor activates
adenylyl cyclase through Gs [6]. 
 
ADRENRGCB1AR is a 7-element fingerprint that provides a signature for the
beta-1 adrenergic receptors. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved sections
within either loop or N- and C-terminal regions, focusing on those areas
of the alignment that characterise the beta-1 adrenergic receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motifs 
1 and 2 span the N-terminus; motifs 3 and 4 lie in the third cytoplasmic
loop; motif 5 spans the third external loop; and motifs 6 and 7 lie at the
C-terminus. A single iteration on OWL28.1 was required to reach convergence,
no further sequences being identified beyond the starting set. Three partial
matches were also found: SSU56425 and S40503 are both beta-1 adrenergic
receptor fragments; and B1AR_MELGA is the turkey beta-T adrenergic receptor
whose sequence differs markedly from those of the rest of the beta-1
receptor family.
 
An update on SPTR37_9f identified a true set of 6 sequences, and 1
partial match.
Summary Information
   6 codes involving  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
76666666
60000000
50000000
40000000
30101100
20000000
1234567
True Positives
B1AR_CANFA    B1AR_HUMAN    B1AR_MACMU    B1AR_MOUSE    
B1AR_PIG B1AR_RAT
True Positive Partials
Codes involving 3 elements
B1AR_MELGA
Sequence Titles
B1AR_CANFA  BETA-1 ADRENERGIC RECEPTOR - CANIS FAMILIARIS (DOG). 
B1AR_HUMAN BETA-1 ADRENERGIC RECEPTOR - HOMO SAPIENS (HUMAN).
B1AR_MACMU BETA-1 ADRENERGIC RECEPTOR - MACACA MULATTA (RHESUS MACAQUE).
B1AR_MOUSE BETA-1 ADRENERGIC RECEPTOR - MUS MUSCULUS (MOUSE).
B1AR_PIG BETA-1 ADRENERGIC RECEPTOR - SUS SCROFA (PIG).
B1AR_RAT BETA-1 ADRENERGIC RECEPTOR - RATTUS NORVEGICUS (RAT).

B1AR_MELGA BETA-1 ADRENERGIC RECEPTOR (BETA-T) - MELEAGRIS GALLOPAVO (COMMON TURKEY).
Scan History
OWL28_1    1  25   NSINGLE    
SPTR37_9f 3 20 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
EPGNLSSAAPLPDGVATAAR B1AR_MACMU 12 12 -
EPCNLSSAAPLPDGAATAAR RATB1ARA 12 12 -
EPCNLSSAAPLPDGAATAAR B1AR_RAT 12 12 -
EPCNLSSAAPLPDGAATAAR B1AR_MOUSE 12 12 -
EPGNLSSAAPLPDGAATAAR B1AR_HUMAN 12 12 -

Motif 2 width=21
Element Seqn Id St Int Rpt
ASLLPPASESPEPLSQQWTAG B1AR_HUMAN 40 8 -
ASLLPPASEGSAPLSQQWTAG B1AR_RAT 40 8 -
ASLLPPASEGSAPLSQQWTAG RATB1ARA 40 8 -
ASLLPPASEGSAPLSQQWTAG B1AR_MOUSE 40 8 -
ASLLPPASEGPEPLSQQWTAG B1AR_MACMU 40 8 -

Motif 3 width=19
Element Seqn Id St Int Rpt
DSCERRFLGGPARPPSPSP B1AR_HUMAN 259 198 -
DSCERRFLSGPPRPPSPAP RATB1ARA 259 198 -
DSCERRFLTGPPRPPSPAP B1AR_RAT 259 198 -
DSCERRFLGGPARPPSPEP B1AR_MOUSE 259 198 -
DSCERRFLGGPARPPSPSP B1AR_MACMU 259 198 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LANGRSSKRRPSRLVALR B1AR_MOUSE 290 12 -
LVNGRAGKRRPSRLVALR B1AR_MACMU 304 26 -
LANGRSSKRRPSRLVALR RATB1ARA 290 12 -
LANGRAGKRRPSRLVALR B1AR_HUMAN 301 23 -
LANGRSSKRRPSRLVALR B1AR_RAT 290 12 -

Motif 5 width=19
Element Seqn Id St Int Rpt
VKAFHRDLVPDRLFVFFNW RATB1ARA 335 27 -
VKAFHRDLVPDRLFVFFNW B1AR_RAT 335 27 -
VKAFHRDLVPDRLFVFFNW B1AR_MOUSE 335 27 -
VKAFHRELVPDRLFVFFNW B1AR_HUMAN 346 27 -
VKAFHRELVPDRLFVFFNW B1AR_MACMU 349 27 -

Motif 6 width=20
Element Seqn Id St Int Rpt
RRAAHGDRPRASGCLARAGP RATB1ARA 390 36 -
RRAAHGDRPRASGCLARAGP B1AR_RAT 390 36 -
RRAAHGDRPRASGCLARAGP B1AR_MOUSE 390 36 -
RHATHGDRPRASGCLARPGP B1AR_HUMAN 401 36 -
RHAAHGDRPRASGCLARPGP B1AR_MACMU 404 36 -

Motif 7 width=19
Element Seqn Id St Int Rpt
GATPPARLLEPWAGCNGGT RATB1ARA 425 15 -
GTTPPARLLEPWTGCNGGT B1AR_MOUSE 425 15 -
GATQPARLLEPWAGCNGGA B1AR_MACMU 440 16 -
GATPPARLLEPWAGCNGGA B1AR_HUMAN 437 16 -
GATPPARLLEPWAGCNGGT B1AR_RAT 425 15 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
EPCNLSSAAPLPDGAATAAR B1AR_RAT 12 12 -
EPCNLSSAAPLPDGAATAAR B1AR_MOUSE 12 12 -
EPGNLSSAAPLPDGAATAAR B1AR_HUMAN 12 12 -
EPGNLSSAAPLPDGVATAAR B1AR_MACMU 12 12 -
EPCNLSSAAPLPDGAATAAR B1AR_PIG 12 12 -
EPCNLSSAAPLPDGAATAAR B1AR_CANFA 12 12 -

Motif 2 width=21
Element Seqn Id St Int Rpt
ASLLPPASEGSAPLSQQWTAG B1AR_RAT 40 8 -
ASLLPPASEGSAPLSQQWTAG B1AR_MOUSE 40 8 -
ASLLPPASESPEPLSQQWTAG B1AR_HUMAN 40 8 -
ASLLPPASEGPEPLSQQWTAG B1AR_MACMU 40 8 -
ASLLTPASEGSVQLSQQWTAG B1AR_PIG 40 8 -
ASPLAPTSEGPAPLSQQWTAG B1AR_CANFA 40 8 -

Motif 3 width=19
Element Seqn Id St Int Rpt
DSCERRFLTGPPRPPSPAP B1AR_RAT 259 198 -
DSCERRFLGGPARPPSPEP B1AR_MOUSE 259 198 -
DSCERRFLGGPARPPSPSP B1AR_HUMAN 259 198 -
DSCERRFLGGPARPPSPSP B1AR_MACMU 259 198 -
DSCERRFLGSPARPPSPAP B1AR_PIG 258 197 -
DSCERRFLGGPARPPAPPP B1AR_CANFA 259 198 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LANGRSSKRRPSRLVALR B1AR_RAT 290 12 -
LANGRSSKRRPSRLVALR B1AR_MOUSE 290 12 -
LANGRAGKRRPSRLVALR B1AR_HUMAN 301 23 -
LVNGRAGKRRPSRLVALR B1AR_MACMU 304 26 -
VANGRTSKRRPSRLVALR B1AR_PIG 291 14 -
LANGRVGRRRPSRLVALR B1AR_CANFA 298 20 -

Motif 5 width=19
Element Seqn Id St Int Rpt
VKAFHRDLVPDRLFVFFNW B1AR_RAT 335 27 -
VKAFHRDLVPDRLFVFFNW B1AR_MOUSE 335 27 -
VKAFHRELVPDRLFVFFNW B1AR_HUMAN 346 27 -
VKAFHRELVPDRLFVFFNW B1AR_MACMU 349 27 -
VKAFHRDLVPDRLFVFFNW B1AR_PIG 336 27 -
VKAFHRDLVPDRLFVFFNW B1AR_CANFA 343 27 -

Motif 6 width=20
Element Seqn Id St Int Rpt
RRAAHGDRPRASGCLARAGP B1AR_RAT 390 36 -
RRAAHGDRPRASGCLARAGP B1AR_MOUSE 390 36 -
RHATHGDRPRASGCLARPGP B1AR_HUMAN 401 36 -
RHAAHGDRPRASGCLARPGP B1AR_MACMU 404 36 -
SCAAAGDGPRASGCLAVARP B1AR_PIG 391 36 -
SHGAAGDPPRARPPPSPGAA B1AR_CANFA 398 36 -

Motif 7 width=19
Element Seqn Id St Int Rpt
GATPPARLLEPWAGCNGGT B1AR_RAT 425 15 -
GTTPPARLLEPWTGCNGGT B1AR_MOUSE 425 15 -
GATPPARLLEPWAGCNGGA B1AR_HUMAN 437 16 -
GATQPARLLEPWAGCNGGA B1AR_MACMU 440 16 -
GAAPPAPLLEPWAGYNGGA B1AR_PIG 428 17 -
GAAPPARLLEPWAGCNGGA B1AR_CANFA 433 15 -